Many longitudinal studies often require jointly modeling a biomarker and an event outcome, in order to provide more accurate inference and dynamic prediction of disease progression. Cystic fibrosis (CF) studies have illustrated the benefits of these models, primarily examining the joint evolution of lung-function decline and survival. We propose a novel joint model within the shared parameter framework that accommodates nonlinear lung-function trajectories, in order to provide more accurate inference on lung-function decline over time and to examine the association between evolution of lung function and risk of a pulmonary exacerbation event recurrence. Specifically, a two-level Gaussian process is used to estimate the nonlinear longitudinal trajectories and a flexible link function is introduced for a more accurate depiction of the binary process on the event outcome. Bayesian model assessment is used to evaluate each component of the joint model in simulation studies and an application to longitudinal data on patients receiving care from a CF center. A nonlinear structure is suggested by both the longitudinal continuous and binary evaluations. Including a flexible link function improves model fit to these data. The proposed hierarchical Gaussian process model with a flexible power link function where Laplace distribution is the baseline (spep) has the best fit of all joint models considered, characterizing how accelerated lung-function decline corresponds to increased odds of experiencing another pulmonary exacerbation. This article is protected by copyright. All rights reserved.

中文翻译：

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联合分层高斯过程模型中的灵活链接函数

许多纵向研究通常需要对生物标志物和事件结果进行联合建模，以便对疾病进展提供更准确的推断和动态预测。囊性纤维化 (CF) 研究已经说明了这些模型的好处，主要检查了肺功能下降和生存的联合演变。我们在共享参数框架内提出了一种新的联合模型，该模型适应非线性肺功能轨迹，以便更准确地推断肺功能随时间的下降，并检查肺功能演变与肺恶化事件风险之间的关联复发。具体来说，使用两级高斯过程来估计非线性纵向轨迹，并引入灵活的链接函数以更准确地描述事件结果的二元过程。贝叶斯模型评估用于评估模拟研究中关节模型的每个组成部分，以及对接受 CF 中心护理的患者的纵向数据的应用。纵向连续和二元评估均建议非线性结构。包括一个灵活的链接功能可以提高模型对这些数据的拟合度。所提出的分层高斯过程模型具有灵活的功率链接函数，其中拉普拉斯分布是基线（spep），具有所有考虑的联合模型的最佳拟合，表征加速肺功能下降如何对应于经历另一次肺部恶化的几率增加。本文受版权保护。版权所有。